 Should Tylenol be avoided as a morning after cure for a night before drinking? Acetaminophen, the active drug in Tylenol, is bad news for the liver if you take too much of it. The same is true for alcohol, so together, do they join forces to really mess things up for you? In many cases the answer is yes, but interestingly, the science behind this drug cocktail combination is not as obvious as you might think. Both acetaminophen and ethanol, the active ingredient in alcoholic drinks, are removed from your body through the process of metabolism. When faced with a substance that's hard to handle, your body produces enzymes to transform it into chemicals that are easier to get rid of. And as we're rather efficient organisms, it's not surprising that there are usually multiple metabolic pathways for getting rid of tough substances like acetaminophen and ethanol. The trouble is, some of these pathways lead to intermediate chemicals that are in themselves harmful. And this is what happens with acetaminophen. Acetaminophen is metabolised in the liver quite effectively through three different pathways. One of these involves an enzyme named CYP2E1. As you can see, toxicologists have a flair for the dramatic when naming substances. As CYP2E1 metabolises acetaminophen, it forms the rather toxic compound NAPQI. This is not something you want to have floating around your body. Fortunately, NAPQI is rapidly dealt with by a powerful antioxidant going by the name of glutathione or GSH. This is all good news for anyone taking Tylenol. But the kicker is that the body can only produce so many of these antioxidants. And so when the antioxidant GSH is all used up, the toxic NAPQI begins to build up and liver cells start to die. So what has this got to do with alcohol consumption? Ethanol is similarly dealt with in the liver by the same CYP2E1 enzyme, which means that if you have both ethanol and acetaminophen in your system, there are competing demands for a limited supply of the enzyme. And this is where things get interesting. If you aren't a regular drinker, when you do have a drink, your liver will start using CYP2E1 to get rid of the ethanol. If you pop a couple of Tylenol a few hours later to take the edge off your hangover, the chances are there's not going to be that much CYP2E1 left to handle it, as the ethanol has mopped up most of what your body can produce. Instead, the alternative acetaminophen metabolic pathways kick in. As a result, less of the toxic NAPQI is produced and some of the toxic side effects of acetaminophen are suppressed. In other words, the science indicates that the occasional drink may actually decrease the very real dangers of acetaminophen overdose. But if you drink a lot and drink regularly, things look very different. In this case, you've trained your body to produce more CYP2E1 and to produce it more regularly, which means that at any given time there's more of it likely to be around to transform acetaminophen into the harmful NAPQI. Even worse, ethanol reduces the rate at which the NAPQI-reducing GSH is produced and liver damage becomes more likely. The bottom line is that taking multiple drugs together can have complex and not always obvious consequences. In this case, the science suggests that an occasional night of social drinking with friends might actually curb the potential harm associated with taking too much acetaminophen. On the other hand, combining acetaminophen with a chronic drinking habit or binge drinking is most definitely bad news for your liver. Of course, as a safer alternative, you could always ditch the Tylenol for some other painkiller or even ease back on the ethanol. Now there is a radical idea.